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spk07: Good morning, ladies and gentlemen, and welcome to the TFF Pharmaceuticals Second Quarter 2023 Corporate Update and Earnings Conference Call. As a reminder, this conference is being recorded. I'll now turn the call over to your host, Corey Davis of LifeSci Advisors. You may begin your conference.
spk01: Thank you, operator. Hello, everyone, and welcome to TFF Pharmaceuticals Second Quarter 2023 Corporate Update and Earnings Conference Call. With me on the line this afternoon are Dr. Harlan Weissman, Chief Executive Officer of TFF Pharmaceuticals, Dr. Zamaneh Mekak, Chief Medical Officer, and Kirk Coleman, Chief Financial Officer. Before we get started, I would like to remind everyone that this call will contain forward-looking statements, including without limitation statements about the anticipated timing of achievement of clinical milestones, the potential to see positive effects in our phase two studies, the number of treated patients necessary to make our decisions in regards to moving to phase three studies, the market opportunity for our product candidates, and the expected timeframe for funding operations with cash and cash equivalents. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially from the statements made. Factors that could cause actual results to differ are described in all of our findings with the U.S. Securities and Exchange Commission. including the risk factor section of our 2022 annual report on Form 10-K filed with the SEC. And now it's my pleasure to turn the call over to Dr. Harlan Weissman. Harlan? Thank you, John.
spk09: And good morning, everyone. And thank you for joining us for our second quarter 2023 corporate update and earnings conference call. On today's call, I'm going to review the significant progress that we've made over the first half of 2023, and then provide an outlook on what we expect to achieve for the remainder of the year. Following my remarks, our Chief Medical Officer, Dr. Zalmanay Mekak, will provide an update on TFS clinical stage programs. Our Chief Financial Officer, Kirk Coleman, We'll then review our financial results for the second quarter. We'll then open up the call for Q&A. In early February, soon after my appointment as TFS permanent CEO, we held an investor call to review our corporate strategy and outline our objectives for 2023. On that call, we expressed our commitment to grow shareholder value by prioritizing the advancement of our clinical stage assets, TFF 4E and TFF TAC. We also expressed a desire to remain opportunistic with respect to signing new partnerships that showed the potential to create long-term value while also minimizing internal costs to our company. It's been nearly six months since that call, and I can say that I'm proud of the company's progress on both fronts. Under Zaminet's leadership, our clinical development team has made considerable progress across a number of key areas to help build physician and patient awareness of TFF-4E and TFF-TAC. Based on the continued success of these efforts, we anticipate reaching key clinical milestones by year end. each of which could serve as a major catalyst for our company. In a moment, the nominee will provide greater details on each of these rare disease programs. We will also have sufficient capital to reach these milestones. As announced earlier this morning, TFF raised additional capital through an equity financing. Importantly, no warrants were issued to investors in this transaction. Considering the ongoing challenges in the capital markets, our ability to close this financing while minimizing dilution to our existing shareholders, in my view, reflects a growing recognition of the attractive risk-reward of our two clinical programs. In contrast to programs involving new chemical entities, TFF-4E and TFF-TAC couple significant innovation with reduced clinical development risk. The innovation is driven, of course, by our thin-film freezing technology that enables efficacious levels of boriconazole and tacrolimus to be delivered directly into the lungs. Through this improved delivery, we expect to see strong efficacy but with lower toxicity and drug-drug interactions compared to systemic delivery. Positions have told us that they would welcome these types of solutions to improve overall care in these highly vulnerable patient populations. We also believe each program bears significantly less clinical risk compared to other development stage programs. By improving the delivery of two well-established first-line FDA-approved drugs, we expect to see positive treatment effects for most of the patients enrolling in our ongoing phase two trials. For this reason, I believe TFF represents a compelling opportunity for investors who seek an optimal balance of innovation coupled with lower overall clinical development risk. Developing new therapies like TFF Worry and TFF TAC that can efficiently deliver an effective drug while lowering systemic toxicities is likely to have a significant positive impact on overall patient health, clinical outcomes, and health economics. Given the size of the patient population, the level of unmet need, the economic burden of each disease, and the anticipated impact of TFF-Vory and TFF-TAC on clinical outcomes, We believe each product represents a $1 billion plus market opportunity. While advancing our pipeline remains our primary strategic objective, I'm also pleased to note that business development at TFF remains quite active. We announced three separate government collaborations during the quarter, which provide third-party validation of the value of our thin-film freezing technology. In May, we signed a cooperative research and development agreement, or CRADA, with the National Institute of Environmental Health Sciences, part of the National Institutes of Health, to develop dry powder formulations of hyaluronan to prevent and treat respiratory diseases. NIEHS and TFF will evaluate the pharmacokinetics and therapeutic efficacy of TFF hyaluronan formulations using in vitro and in vivo models of select respiratory diseases, with a primary focus on chronic obstructive pulmonary disease, or COPD, and viral respiratory diseases caused by SARS-CoV-2, influenza virus, and or respiratory syncytial virus, or RSV. Also in May, we signed a contract extension with Leidos that provides additional funding to advance next generation personalized protective biosystems under the personalized protective biosystems program managed by the Defense Advanced Research Projects Agency, more commonly referred to as DARPA. The goal of the program is to develop lightweight materials using thin-film freezing technology that protects military and healthcare personnel from exposure to chemical and biological threats. In June, we announced an agreement with the National Institute of Allergy and Infectious Diseases, also part of the National Institutes of Health, that awarded TFF Pharmaceuticals a direct to phase two small business innovation research or SBIR grant of approximately $3 million to continue development of a shelf-stable universal influenza mucosal vaccine using the company's thin-film freezing technology. The aim of this program is to develop a vaccine that is at least 75% effective against symptomatic influenza virus infection. Importantly, these agreements are largely funded by our partners. and provide an important source of external validation for our technology. I'd now like to turn the call over to Dr. Zamaneh Mekak to discuss the TFF-4E and TFF-TAC clinical programs.
spk10: Zamaneh?
spk08: Thank you, Harlan. As Harlan mentioned, I'm pleased to share with you the considerable progress we're making to advance enrollment in our two phase two trials of TFF-TAC and TFF-4E. Over the last several months, our clinical development team has undertaken multiple initiatives to advance these programs. I'll start by providing an update on TFF-4E. As a reminder, TFR-4E has been formulated using our thin-film freezing technology to deliver antifungal drug ibuprofen directly to the lungs. TFR-4E is being developed for potential treatment of pulmonary fungal infections, including pulmonary aspergillosis, starting with invasive pulmonary aspergillosis, or IPA. IPA is a life-threatening fungal lung infection that primarily impacts immunocompromised patients. With standard of care therapy, the 12-week mortality rate from IPA is approximately 30%, which represents a significant unmet medical need for this rare disease. Oral loriconazole is first-line therapy for treatment of IPA, but because of the drug's narrow therapeutic window, attaining efficacious concentrations often requires dosages that cause significant toxicities. By administering TFF worry directly into the lungs, we hope to improve efficacy by delivering high local concentrations of the drug while lowering systemic exposures and therefore systemic toxicities and drug-drug interactions, problems commonly associated with oral administration. As Harlan mentioned earlier, we have made considerable progress over the last several months. We established weekly goals for our CRO and weekly meetings with CRO upper management. We improved accountability and overall execution, and these changes have helped considerably. For example, we now have 16 of our 19 clinical sites activated compared to only a single site when I first joined TFF back in January. We expect additional sites to be up and running this quarter. Various of the TFF worry program is growing among hematologists, oncologists, infectious disease physicians, pulmonologists, and transplant physicians at our active clinical sites and their referral networks, which in turn is leading to an acceleration in patient prescreening and screening activities. As a result, our rate of prescreening has increased nearly fivefold in the past four months compared to the first four months from 9 to 44, and we now have two patients enrolled in our study. Additionally, we have amended the study protocol to improve patient access to TFF40. For example, based on feedback from our investigators, we have expanded eligibility to allow real-world criteria used for the diagnosis of IPA. In a disease with high unmet need, in which first-line therapy is associated with high mortality, toxicity, and drug-drug interactions, Patients often choose to participate in a clinical trial with the hope of receiving an investigational drug with potential for improved efficacy and or toxicity. To improve the chances of receiving TFF4E, we have also increased the ratio of patients receiving TFF4E to those receiving oral variconazole from 1 to 1 to 3 to 1 in this study. While we're developing TFF4E for the potential treatment of IPA by conducting clinical trials, We understand that in some cases, patients who have exhausted available therapeutic options may not qualify for participation in clinical trials. For such cases, we have launched an Expanded Access Program, or EAP, offering TFR-40 to patients with all forms of pulmonary aspergillosis, including both invasive and chronic pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, Aspergillus tracheobronchitis, and Aspergillus bronchoanastomotic infections. Patients with other voriconazole-responsive pulmonary infections also qualify for this program. The patients who enter our EAP have limited or no treatment options, or in some cases have had an unfavorable response to standard of care therapy. The EAP program builds on the positive efficacy, safety, and tolerability results in two such patients with pulmonary fungal infections who were previously treated with TFF4E on a compassionate use basis. I'm also pleased to note our collaboration with Derby to help us implement the EAP for TFF4E in the US, Canada, Australia, UK, and select countries in the EU. Durbin has a long track record of executing expanded access programs across the globe for large and small pharma companies, and we are confident that through this partnership, we will be able to provide expanded access to TFR4E to eligible patients. In fact, I am pleased to note that we have already enrolled our first patient in this new program. As Harlan mentioned, we expect to see a majority of patients who receive TFR4E therapy to show a positive treatment effect due to the well-established activity of vericonazole as an antifungal medication. Given the availability of considerable historical data on the safety, tolerability, and efficacy of vericonazole, and in line with what is generally customary in rare disease indications, We believe no more than 10 patients treated with TFF4E may be necessary to provide us with enough clinical data to make a go-no-go decision on entering a Phase 3 trial. Initial data from our ongoing Phase 2 trial and EAP are expected by the end of 2023. Now, let me turn to discussing the TFF tax Phase 2 program. Similar to TFF-4E, the TFF-TAC program addresses an area of significant unmet medical need in another rare disease indication. TFF-TAC is being developed for prevention of rejection in lung transplant recipients, a patient population with a five-year mortality rate as high as 50%. The 50% five-year mortality in lung transplant comes largely from the narrow therapeutic window of available immunosuppressants, where too little immune suppression leads to acute or chronic rejection, whereas too much immune suppression leads to infection, chronic kidney disease, and post-transplant lymphoma or other malignancies. To overcome these deficiencies, TFF-TAC has been formulated using our thin-film freezing technology to deliver the first-line calcineurin inhibitor immunosuppressant drug to columnists directly to the lungs. The direct delivery of TFF-TAC to the lungs is poised to potentially address multiple contributing factors to the 50% five-year mortality seen in lung transplants. With local delivery to the lungs, the ratio of lung exposure to systemic exposure increases. Therefore, lung concentrations sufficient to drive efficacy locally can be achieved at lower doses compared to oral administration, leading to lower systemic exposures to minimize systemic toxicity. The improved lung to systemic exposure achieved with TFF-TAC is predicted to address the fine balance needed for immune suppression. The improved concentrations in the lung, the site of inflammation, would address acute and chronic rejection, while diminished systemic exposures would address potentially fatal complications such as infections, chronic kidney disease, and post-transplant, lymphoma, or other malignancies. It should be noted that presence of systemic exposure, albeit at lower levels compared to oral to colonists, is predicted to suppress systemic inflammation to further prevent rejection. In our phase two trial, we have gained considerable insights at our active site in Australia in transitioning lung transplant patients from oral to colomus to the inhaled form TFF-TAC. The transition from oral to inhaled to colomus is a delicate process given the risk of rejection and toxicities. We have been pleasantly surprised by the low doses of TFF-TAC needed to date to match overall clinical outcomes from oral to columnar. To date, three patients have enrolled in the Phase II study at our active site. We expect to activate additional sites in Australia in the coming months. Since our selected sites have a large database of lung transplant patients that could be considered for potential enrollment in our study, we expect a steady flow of patients in our TFF FACT study. Similar to the TFF BORI program, Given the availability of considerable historical data on the safety, tolerability, and efficacy of tacrolimus, and in line with what is general practice in rare indications, we believe meaningful clinical data from approximately 10 patients treated with TF-ACTAT will be sufficient to guide a go-no-go decision for entering a Phase III study, and we expect to report initial data from the ongoing Phase II study by the end of 2023. I'll now turn the call over to Kirk to review our second quarter financial results.
spk00: Thanks very much, Amine. Our cash and cash equivalents as of June 30, 2023, were $7.7 million. The additional proceeds from the financing transaction announced earlier today will ensure that we have sufficient resources to reach anticipated upcoming clinical milestones and will extend our cash runway through the first quarter of 2024. Research and development expenses for the second quarter of 2023 were $2.7 million compared to $5.1 million for the comparable period in 2022. $2.4 million decrease year-over-year is primarily a result of reduced clinical and manufacturing expenses. General administrative expenses for the second quarter of 2023 were $2.7 million compared to $3.7 million for the comparable period in 2022. $1 million decrease year-over-year is primarily related to decreased professional fees and patent expenses, insurance, consulting, market research, and payroll and payroll-related expenses. Net loss for the second quarter of 2023 of $5 million compared to a net loss of $8.7 million for the comparable period in 2022. Tarlin noted previously, We have been focused on spending responsibly as we progress our clinical trial programs. I am proud of the team for successfully reducing spending in areas that were not part of the primary strategic objectives. I'll now turn the call back over to Harlan.
spk10: Thank you, Kirk.
spk09: Before opening up the call for questions, I would like to express my sincere thanks to Zominay and her team for all of their hard work and dedication. which has enabled us to make significant progress across multiple fronts in our TFF TAC and TFF VORI programs. Since becoming CEO six months ago, my confidence in the therapeutic and commercial value of these two assets has only continued to grow. By improving drug delivery with our thin-film freezing technology, the VORI and TAC programs have the potential to demonstrate a transformative impact in two rare disease indications by effectively restoring the full efficacy potential of lifesaving medicines. Moreover, each addresses areas of significant unmet medical need in rare disease indications with sizable patient populations and substantial market opportunity. If we succeed in this endeavor, I'm equally confident that the value of our technology platform, internal pipeline, and partnerships will be increasingly recognized in the market, providing investors with the opportunity to reassess the value of our company in the months ahead. That concludes our formal remarks. And I'd like now to open the call up for the question and answer session. Operator?
spk07: Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the one on your touchtone phone. You will hear a three-tone prompt acknowledging your request. If you are using a speakerphone, please lift the handset before pressing any keys. First question comes from Jonathan Ashoff of Roth MKM. Please go ahead.
spk04: Thank you very much. My first question, guys, is about BORI. You know, given that there's only two patients in the trial, what gives you the confidence that you can meet that 10-patient expectation by year-end? And I guess this explains the, you know, two-to-one ratio of sites to intended patients.
spk09: Jonathan, hi, and good morning, and thank you for the question. You know, the clinical trial has been ramping up since Zaminet took over as chief medical officer. And it is a process that takes a while to overcome the initial inertia in the clinical trial. But we're now, as Zaminet went over in her remarks, seeing that progress. And I'll ask Zaminet to comment further on answering your question.
spk08: Hi, Jonathan. Hi. Thanks for the question. You know, as I mentioned, we have made a significant level of progress. We now have 80% of our sites activated, 16 sites in Europe, in five different countries. Our investigators are engaged. Our protocol eligibility has been expanded to allow patients that meet real-life criteria for diagnosis of IPA And because we've changed the randomization schedule such that instead of one-to-one, patients have the opportunity to receive TFF4E with a three-to-one chance, the trial is a lot more inviting to patients who would consider participation. All of this momentum, we believe, is setting us up to bring the number of patients that we are projecting and to have initial data by the end of the year.
spk04: You know, with the height, can you tell me, I mean, you know, up five-fold in the past four months, but to only have two patients, you know, what's the explanation for so few patients qualifying for this trial?
spk08: That's a good question. IPA is a fatal disease. So one of the things that we're noticing is that because it's such a severe disease, you have severe fungal infection on top of, for example, hematologic malignancy. This is a patient, say, with leukemia, a type of leukemia, who now has a fungal infection. It's quite a fatal disease. What we've noticed is that many of the patients who are considered for the clinical trial actually end up in hospice or palliative care. You know, they're quite ill and that's why they don't qualify. Another reason that they might not qualify is that the diagnosis ends up not being aspergillus or not being exactly IPA or they're not meeting the very specific and very narrow criteria for diagnosis of IPA based on the original diagnostic criteria that was in the protocol, which we've kept. But again, we expanded that to include real-life criteria, and we believe that improves eligibility and study participation. As I mentioned, we have a lot of sites active now, and the investigators are quite engaged. But at the end of the day, we want to make sure we get the right patients in this study. I think the other thing to really keep in mind is that what do you accomplish, what can you accomplish while you're setting things up, and what can you accomplish once you have set things up? So we have brought in the number of patients that we've brought in as we've been activating sites, as we've been putting in an addendum, as we've been putting in an amendment. But doing that requires a lot of steps to actually implement these changes. Now we're at a point where the sites are active. The amendment is in place and approved in almost every country. The sites are familiar with these broadening eligibility criteria, and they understand how that impacts their evaluation of patients. So that's why looking at the activities on the ground and the information we have, we're comfortable to project that we'll be able to have initial data by the year end.
spk04: Thanks for that. You know, what was flawed about 40 patients as an enrollment number for VORI such that, you know, 10? can allow you to come up with a go, no-go decision for phase three?
spk08: That's a good question, too. You know, the 40-patient trial was the original design of this study, really did not take into account that the indication, IPA, is a rare disease. You do a 40-patient phase two study, for example, in rheumatoid arthritis. if you're doing a, you know, sort of a regular POC, or you do it in psoriasis, you know, a big common, you know, big footprint disease. In rare diseases, generally, you look for a smaller sample size in your trials because there are just much fewer patients in these trials. For example, IPA, the number of patients with new diagnosis of IPA worldwide is 80,000 patients. So that's quite a rare disease. So the way one does clinical development in a rare disease indication is that you look for more telling signals of efficacy, and that helps you have a smaller sample size. We also have the luxury that the drugs we're developing are first-line approved drugs. The chemical entities are not new. So we know what boriconazole can do. We know what tacrolimus can do. We understand their efficacy profile. we understand their safety and tolerability profile. So we don't think you need 40 patients to be able to make a call as to how TFF40 is doing compared to oral voriconazole. You know, I'll give you an example. With oral voriconazole, about 15 to 20% of patients have to decrease their dose or actually eventually go off therapy because of liver toxicity. That's a really high rate of liver toxicity, and that's very well known, very common experience. In our clinical trials, we have not seen any patients so far between the healthy volunteers, between patients with mild asthma, between the patients we've had in compassionate use, between the patients we've had so far in our clinical trial, nobody with liver toxicity. So, we don't think you're going to need 40 patients to be able to make this call. The difference will be large enough that you'll be able to make a call with just 10 patients. So, it's really an adjustment in clinical trial design to match the indication a little bit better.
spk04: Okay. So, you will make that decision on 10 patients versus, you know, 10 doesn't quite look compelling. Hey, let's enroll more. Like, what do you think you're more likely to do? Just make that call or... You know, if that's not clearly a yes, you know, try for some more patients to see if it gets to a yes.
spk08: You know, we've always said it's approximately 10 patients. But bottom line is that we don't think you need a lot more than that. You know, obviously, you have to look at your data, make decisions accordingly. But we don't think you'll be. You need the original design, which was comparing 20 patients getting TFS4E with 20 patients getting oral voriconazole and then making a call. We think we'll be able to really rely and draw on the experience that the knowledge that's there about oral voriconazole, and also you would need fewer patients than 20 to make a call about TFR40.
spk04: Okay, and not to leave Kirk out. Kirk, there were sequential questions. decreases, which is good in R&D and SG&A for the first and the second quarter. Are you at a cruising altitude, or do you expect that to continue dropping a little?
spk00: That's a great question, Jonathan. Thank you. I think we are starting to settle in, and the guidance we're given, obviously, is we're anticipating that our burn rate is about $4 million a quarter, and we've got enough runway to get us through into Q1 of 2024.
spk04: Yeah, I've got you there easily. Okay, thank you very much.
spk00: Thank you very much. Thank you.
spk04: Thank you, Jonathan.
spk07: Thank you. The next question comes from Justin Walsh of Jones Trading. Please go ahead.
spk06: Hi, thanks for taking the questions. Can you expand on the criteria you expect to use for your go, no-go decisions? What type of results would you need to see to give you confidence that it warrants advancing into Phase 3 for either asset?
spk09: Yeah, good morning, Justin, and thank you for the question. That one seems like another perfect one for Zomide to address.
spk08: Thank you, Justin. So, we will look at signals of efficacy. For example, in TFA4, you certainly want to see that patients are feeling better. The clinical signs and symptoms have improved, and we like to see that there is evidence that the aspergillus has been cleared. The treatment duration is about 12 weeks. That may or may not be long enough to see radiologic evidence, but we certainly look for it and we expect to see that at least in some patients. In the TFF-TAC program, for example, we want to make sure that as we transition patients from the oral tacrolimus to the inhaled tacrolimus, we continue to see that patients are free of rejection. and that they're shown good signs of safety and tolerability. And, of course, safety and tolerability is big for TFF4E as well.
spk06: Got it. And did you have discussions with the FDA or the EMA related to the amendment of the trial?
spk08: We made the amendment and we submitted it to the health authorities in the various countries we're in, in Europe, and they've been approved in four out of five countries, and it's under review in the fifth country.
spk06: Got it. And then last question for me, you had mentioned the hospice and some of that angle here, but I'm just wondering if you can remind us or provide commentary on the expanded access and compassionate use of TFF-Vory. What alternatives do these patients face, either in terms of standard of care or other experimental therapies that you might be aware of?
spk08: The expanded access program really provides the opportunity for patients who might benefit from TFF-Vory to get access to it. And the patients who might benefit from this therapy are not just patients who have invasive pulmonary aspergillosis. There are many other indications for which TFF4E could be helpful. Chronic pulmonary aspergillosis, ABPA, you know, in patients with lung transplant, bronchial anastomotic infections. There are many areas. And also fungal infections that are not aspergillus but are voriconazole sensitive. So every time you do a clinical trial and you have a clinical trial protocol, you have to implement and cement a particular design. And once that design is cemented, then there are patients who don't qualify based on one thing or another. So the expanded access program really helps us get Tiafra 40 in the hands of patients who could potentially benefit from it. And these are patients, like you mentioned, who have tried standard of care therapy at adequate levels and have not had a good response to it or because of systemic toxicities are not able to tolerate these drugs. The two patients we had for compassionate use that were treated previously, for example, were patients who were lung transplant recipients. They had recurrent pulmonary infections, pulmonary fungal infections, and they had significant toxicities to the point that when their infection came back, they were at the end of their rope. didn't know where to go and that's where TFR 40 was given to them with very good results.
spk10: Got it. Did that answer your question? Yes, that does. Thank you.
spk07: Thank you. The next question comes from Vernon Bernardino from HV Wainwright. Please go ahead.
spk10: Your line is open. Please proceed with your question. Sorry, I was muted.
spk03: Your answers as far as the VORI program have been very informative. So, I think I know the answer to my question. Regarding the Phase II TFF TAC program though, do you think that the, small number of patients that are going to be dosed in the TAC clinical trial will be predicted enough to also make a go-no-go decision for Phase 3?
spk10: Why don't you go ahead and take that, Zaminé? Sure. And good morning, Vernon, and thank you.
spk08: Thank you. Yes. Yes. We think just about 10 patients would be sufficient for us to make a call about as well. You know, as I mentioned, we've enrolled 3 patients with our 1st patient. It was the 1st time we were transitioning patients from oral to columnist to inhale to columnist. So we. approaches very conservatively, watching that patient very carefully, making the transition, and then very slowly leaning the dose of inhaled tacrolimus because you have to be careful about that balance of making sure the patient doesn't go into rejection while you're improving prospects of safety and tolerability. And we, as I mentioned, we were surprised of how low we were able to go in the TFF-TAC dose. With the second patient, we implemented our learnings from the first patient and were able to duplicate those observations. So, obviously, we want to see that happening in a number of other patients, but we think approximately 10 patients will be sufficient to give us the information we need to make a call that yes, this is a goal into phase three. And obviously, you continue always to learn from additional patients you bring in all throughout your development program. But approximately 10 patients should be sufficient.
spk03: Okay, great. I look forward to that decision. Now, I know an expanded access program is generally not one designed to provide results, for example. But the expanded access program, especially with your drugs, DFF, Vori, and TAG, but in particular, the Vori Conazole study, as you mentioned, the small number of patients, would there be a possibility to get any kind of data and or results from that program? And would, especially with the help of Durban Ireland, or Unifar rather, provide a perhaps broad coverage of the kind of patients globally that you could, I guess, put together, translate, synthesize, whatever, however you want to describe it. into the results that you might see with TFF-ORI.
spk10: Yeah, why don't you go ahead, Dominique, and take that one too.
spk08: Sure. Yes, we believe that the information we gather through the Expanded Access Program will add to the knowledge base. that we're going to have about TFF4E and its potential. You know, we are developing TFF4E by conducting a clinical trial, and the results of the clinical trial will lead us and help us and guide us to understand our next steps and the design of our Phase III, et cetera. But the information we're gathering through the Expanded Access Program is very valuable and adds to that. It also really expands the indications that we're in. You know, the clinical trial is in basic pulmonary aspergillosis. The expanded access program gives the opportunity for TFF4E to be in five additional indications, which is really significant. So that information is really helpful to us also to understand where are the signals of efficacy where we should be pursuing further clinical trials for TFF4E.
spk09: Yeah, I just wanted to, I'm sorry, just mentioned that you brought up Durbin. And one of the reasons for us signing on with Durbin is that we have, although it's not a formal clinical trial protocol, we do have a data collection mechanism that would provide us with uniformity across the various patients that come into the Compassionate Use Program. So it's not with the same degree of rigor. but there is a systematic data collection that's planned that will allow us to characterize the patients and the outcomes.
spk10: Zalman, I don't know if you want to comment.
spk03: That's exactly what I was looking for. Yeah, terrific. That's exactly what I was looking for. And then secondarily, I know you have cash, as Kirk said, through perhaps third quarter 2024. My model makes it easy to see that that is certainly true. But if you had additional cash, what other molecules do you think you might think about advancing into clinic and make good sense in whether they be small studies or just even proof of concept studies where you could generate results that would provide additional opportunities for our partnerships.
spk09: Yeah, thank you for the question. Just to clarify, it's enough cash to get us through the first quarter of next year, and clearly we're going to have to raise money again based on the expected inflection point from us producing data we think will be a catalyst to allow us to raise more money. The first order of business when we raise money is to be able to continue to fund the development of TFF4E and TFFTAC. So I want to ensure that we don't drop the ball on those two programs and get too unfocused. So that's our initial focus. But as you pointed out, there are other molecules. And we have a process underway to evaluate potential pipeline products. You know, we recently reacquired four rites of niclosamide. I'm not saying we would go forward with that, but we have it, and we are currently evaluating whether it makes sense to go forward with niclosamide and indications besides COVID-19, which was the original idea of it. And we'll evaluate that. But we also have shown that our technology is able to take for example, a large variety of biologics like monoclonal antibodies, vaccines. And, you know, we have the agreement with the NIH to develop a universal flu vaccine and mRNAs and even bacterial phages. And so there's, you know, we have a wealth of different opportunities. The key is going to be to see what we should focus on. And it's premature for me to to say that with any degree of certainty. We really have to go through that evaluation process, which we will get underway, and we have underway right now.
spk10: Perfect. I appreciate the insights and the answers to my questions. Thank you.
spk07: Thank you. The last question comes from Daniel Carlson at Tailwinds. Please go ahead.
spk05: Thank you, and good morning, everyone. Just a couple of follow-up questions regarding the expanded access program. Is that data something you can submit to the regulatory authorities like the FDA or EMA, and will they consider that data when advising on potential next steps?
spk09: Yeah, Dan, first of all, good morning, and thank you for participating. Appreciate the question. We believe the answer is yes, but let me let Zaminé elaborate.
spk08: Hi, Dan. Yes, yes, we believe that will be part of the data package. The expanded access data, after all, is valuable and helpful data about what TFF WARI has been able to do. And the FDA does accept that as part of the data package that one submits.
spk05: Great. Zamaneh, you mentioned for the Phase II VORI expanding the eligibility criteria with additional real-world criteria. Can you just elaborate on what that means exactly?
spk08: Sure. So, with every clinical trial, obviously, you need to make sure that you get the right patients. Because, for example, if the patient doesn't have, let's say, aspergillosis, which responds to boriconazole, then obviously one couldn't expect TFF4E to cause improvement. So it's important to make sure you get the right patients in. The diagnostic criteria, that's part of the protocol that is customarily part of the protocol for IPA-type studies. is a very strict and academic type of diagnostic criteria, which is very valuable. But it is very strict. For example, it includes that the patients have to have certain signs and symptoms to be part of that, to be eligible as part of meeting the criteria. And those signs and symptoms don't include worsening cough. Now, in reality, When physicians say, for example, you know, we're talking about a patient with hematologic malignancy, you have that patient with AML who's now developed a fungal, pulmonary fungal infection. They see that the patient has increased respiratory symptoms, including a productive cough that has worsened, and the chest CT shows a cavity, and they grow aspergillus from their lungs. that patient in the real world gets treated with voriconazole for the probable diagnosis of IPA. But based on that academic set of criteria, that patient wouldn't be considered because worsening cough is not one of the specific signs and symptoms mentioned in that diagnostic criteria. So after talking with our investigators, one of the You know, they gave us feedback about various aspects, and one of the pieces of feedback we received was this, that, you know, in the real world, we actually diagnose patients with IPA, bringing clinical judgment and putting the various parameters together to get a story, get a picture of does this fit IPA or not. And as a result of that, we've brought that into the protocol, allowing these real-world criteria like worsening cough to qualify the patient as long as other elements are met the way they're supposed to be met.
spk05: Got you. I got you. And so, can you just, can you comment at all about your screening failure rate? And will this change that?
spk08: It should. It should. It should, because again, previously, some of the patients that didn't have the specific signs and symptoms mentioned in the algorithm, they would not qualify. And now, because we've entered these real-world criteria into the protocol, they would qualify for study participation.
spk05: Gotcha. Okay. And then one question on TAC. You mentioned that you're surprised how little TFF TAC it takes to match the overall clinical outcome from oral TAC limits. Can you elaborate on that and what that means from a clinical standpoint?
spk08: Yes. So patients come in. These are patients who are lung transplant recipients. They've had their lung transplant some time ago, six months ago or so, or more, years ago. And these are patients who all of them are oral tacrolimus because most patients, most lung transplant recipients do go on oral tacrolimus to control rejection. And they've been on oral tacrolimus long enough to start to have the toxic effects of oral tacrolimus. So these are the patients whose kidneys are shutting down. But the physician is faced with that decision of what do I do with this patient? If I continue the patient on oral tacrolimus at the dosages that I have them on, the kidneys are going to continue to worsen. So I decrease the oral tacrolimus, hoping they don't go into rejection. Maybe I add a different type of immunosuppressant as I decrease oral tacrolimus, but that's going to have its own toxicity. So these are the types of patients right now in this study. So as we take these patients, the patients are doing well from a rejection perspective. They're not rejecting their lungs. Their oral techolomus is keeping rejection at bay, but their kidneys are not functioning well. So we have transitioned these patients. We've learned how to transition, how to take that dose of oral techolomus. and understand what would be an equivalent dose in TFF-TAC to keep the same blood levels. And then from there, we've learned how much can be slowly go down and see that the patients continue to be clinically stable. No clinical signs of rejections, no inhaled tecrolimus TFF-TAC, providing them with the benefits of oral tecrolimus. and then starting to see the beneficial effects of lower toxicity. Obviously, we need to dose many more patients. That's why we think we will need approximately 10 patients to make a final call, but we're just very encouraged. TFF-TAC is also the drug that when we talk with lung transplant doctors, they say this is the drug we've been waiting for. So there's a lot of enthusiasm to hopefully get this drug in the hands of patients and hopefully see how this transition helps with that improved efficacy and lower toxicity parameter. And in the long run, this is a drug that should be used in assuming we show the type of response we're projecting and hoping to see. This is the type of drug that should be used in patients before they develop renal toxicity. There should be no reason for us to wait for patients to develop renal toxicity from oral tecrolimus and then change them to TFF-TAC. So in the long run, our goal would be to really have this available for patients from the start.
spk05: Gotcha. That's exciting. Thank you. And And so I'm going to thank you. It's obviously done a lot of work at turning these programs around. So I want to thank you for your efforts in that regard. Thank you. You've brought a long way in a short time, it appears. So last question for me, Harlan. You know, you focused rightly on the two phase twos, but there were a number of other potential balls out there in the air. And I'm just wondering if there's anything progressing on the on the third-party work that you've been working on in the past, or if that's just sort of all silent now.
spk09: Thank you, Dan, for that question. We still have ongoing collaborations going with some big pharma companies and also biotech companies. It is going on in the background. You know, the one thing we've done is we've changed the emphasis of what we're doing to, you know, throw as much as many hooks out there to catch fish to be more focused and go to the fishing hole where the fish actually are. And so we're saying, one, we've narrowed the focus to be only on those programs that we think we can make a real difference that are business interests to the collaborator that might lead to where we can add value that might lead to a business deal in the future. And the other is that we want people to pay their way completely. Before, we were doing quite a lot of work where we were taking on the burden of the cost. It wasn't tremendous cost, but we were taking on that burden. Now, if somebody wants to collaborate with us, part of demonstrating that it's important to them is for them paying their way. So we have a more narrowed group of collaborations that we have going on. And of course, we have the government collaborations, which we're very excited about. You know, we've received that pays for our laboratory costs, our human resources devoted to those projects. And we're exploring other opportunities on the non-dilutional side of working with government and other organizations.
spk10: Gotcha. Well, thank you. Appreciate it. Thanks for taking my questions. Yeah. Thank you, Dan.
spk07: Thank you. If there are no further questions, I will turn the call back over for closing comments.
spk09: Well, in closing, I'd just like to thank all of you for being on today's call. And I'd especially like to thank all of our investors who've demonstrated their belief in and support of our company. I'm convinced the TFF4E and TFFTAC programs have the potential to significantly advance the current standard of care and their respective rare disease indication. And that's why I, as well as our officers, directors, and employees have purchased significant equity in our company. Thank you again, and we look forward to providing another corporate update in November.
spk07: Ladies and gentlemen, this concludes your conference call for today. We thank you for participating, and we ask that you please disconnect your lines.
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